For decades, oncology research has focused on the search for detectable cancer specific markers, which can be used to verify the presence or absence of cancerous cells of various germlines in a tested biological specimen. Numerous cancer specific markers, including proteins, carbohydrates and nucleic acids, were found and characterized. However, none were shown to be pan-malignant, expressed by or secreted from all or even most cancer cell types. Hence, the quest is ongoing for a universal marker enabling effective oncodetection.
Normal and malignant cells have remarkably different phenotypes. The differences include the ability to form tumors in animal models, different differentiation state, ability to form colony in soft agar, lost of contact inhibition and spreading alterations, a faster metabolic rate and expression of tumor-specific markers.
The most common techniques utilized to detect cancerous cells are immunohistochemistry, immunocytochemistry and in situ hybridization. Those techniques are based on compounds of high affinity to a specific cellular molecule. These technologies are mostly used for phenotypic characterization of tumors (e.g., by implication of antibodies to intermediate filaments), detection of tumor markers of prognostic value (e.g., detection of p53 antigen), as well as the detection of other oncogenic expression features and nucleic acid sequences. Despite the high specificity of these techniques to detect malignancies, none of these techniques provides a pan-malignant tool for oncodiagnosis.
Other diagnostic cytology techniques include a narrow set of staining methods and compositions, some of which appeared many years ago, but are still being extensively used in present clinical cytology. This refers primarily to the alcohol-fixed Papanicolaou stain and the air-dried May-Grunwald-Giemsa (a version of which is known as Romanowsky) stain, while staining with hematoxylin and eosin, Shorr's staining for endocrine cytology and the Pappenheim method are more rarely used. However, those staining procedures are both time consuming and do not reveal any tinctorial selectivity for malignant cells.
It would be of utmost importance to discriminate between normal and malignant phenotype of cells in suspension, by a simple method, not limited to any particular cancer cell type. Particularly, there is an unmet need for differentiation techniques for detecting cancerous or precancerous cells suspended in biological fluids.